title: Role of caveolin-1 in the pathogenesis of tissue fibrosis by keloid-derived fibroblasts in vitro.
abstract: BACKGROUND
  Recent studies have suggested that caveolin-1 (cav-1) plays an important role in the regulation of transforming growth factor (TGF)-β1 signalling and participates in the pathogenesis of tissue fibrosis. However, its effects on dermal fibrosis keloids are unknown.
  
  
  OBJECTIVE
  To investigate the effect of cav-1 in the pathogenesis of tissue fibrosis by keloid fibroblasts.
  
  
  METHODS
  Keloid fibroblasts were cultured and exposed to different concentrations of cav-1 cell-permeable peptides (cav-1p) in the presence of TGF-β1. Keloid fibroblast phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, and multiplex enzyme-linked immunosorbent assay techniques. The effect of cav-1p on cell viability was evaluated by MTT assay.
  
  
  RESULTS
  Cav-1 was markedly decreased in the keloid-derived fibroblasts. Moreover, cav-1p significantly reduced TGF-β receptor type I levels and Smad2/3 phosphorylation in response to added TGF-β1. Additionally, TGF-β1 decreased cav-1 expression in human skin fibroblasts. Cav-1 was able to suppress TGF-β1-induced extracellular matrix production in cultured keloid fibroblasts through regulation of the mitogen-activated protein kinase pathway.
  
  
  CONCLUSIONS
  Cav-1 appears to participate in the pathogenesis of tissue fibrosis in keloid. Restoration of cav-1 function by treatment with a cell-permeable peptide corresponding to the cav-1 scaffolding domain may be a novel therapeutic approach in keloid.
authors.affiliation: Department of Hand and Plastic Surgery, the Second Affiliated Hospital of Wenzhou Medical College, Zhejiang, China. guoyou.zhang@yahoo.com
authors.forename: G-Y
authors.initials: GY
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
authors.forename: T
authors.initials: T
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Liao
authors.forename: C-L
authors.initials: CL
authors.lastname: Nie
authors.forename: A-Y
authors.initials: AY
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: X-G
authors.initials: XG
authors.lastname: Xie
authors.forename: A E
authors.initials: AE
authors.lastname: Albers
authors.forename: W-Y
authors.initials: WY
authors.lastname: Gao
mesh_terms: D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1